Molecular determinants of selective dopaminergic vulnerability in Parkinson's disease: an update.
Molecular determinants of selective dopaminergic vulnerability in Parkinson's disease: an update.
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DOI：
10.3389/fnana.2014.00152
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发表时间：
2014
影响因子：
2.9
通讯作者：
Greengard P
中科院分区：
文献类型：
--
作者：
Brichta L;Greengard P
中枢神经系统（CNS）的许多疾病归因于不同神经元细胞群的选择性死亡。有趣的是，在许多这些情况下，一个特定的神经元子集非常容易变性，而其他非常相似的神经元受到的影响较小，甚至可以存活多年。在帕金森病（PD）中，运动表现主要与黑质丘脑部（SNpc）中多巴胺能（DA）神经元的选择性进行性丧失有关。相反，腹侧被盖区（VTA）中非常相似的DA神经元表现出低得多的变性程度。阐明PD中差异DA脆弱性现象的分子机制已被证明是极具挑战性的。此外，越来越多的研究表明，相当大的分子和电生理异质性之间存在的DA神经元内的SNPC，以及那些在腹侧被盖区，又增加了一层的复杂性，PD中观察到的选择性DA的脆弱性。调节DA神经元对变性的这种差异敏感性的关键通路的发现对于发现新的药物靶点和开发有前途的神经保护治疗策略具有巨大的潜力。本文综述了PD中脑DA神经元差异脆弱性的分子基础，并强调了这一领域的最新进展。
Numerous disorders of the central nervous system (CNS) are attributed to the selective death of distinct neuronal cell populations. Interestingly, in many of these conditions, a specific subset of neurons is extremely prone to degeneration while other, very similar neurons are less affected or even spared for many years. In Parkinson’s disease (PD), the motor manifestations are primarily linked to the selective, progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). In contrast, the very similar DA neurons in the ventral tegmental area (VTA) demonstrate a much lower degree of degeneration. Elucidating the molecular mechanisms underlying the phenomenon of differential DA vulnerability in PD has proven extremely challenging. Moreover, an increasing number of studies demonstrate that considerable molecular and electrophysiologic heterogeneity exists among the DA neurons within the SNpc as well as those within the VTA, adding yet another layer of complexity to the selective DA vulnerability observed in PD. The discovery of key pathways that regulate this differential susceptibility of DA neurons to degeneration holds great potential for the discovery of novel drug targets and the development of promising neuroprotective treatment strategies. This review provides an update on the molecular basis of the differential vulnerability of midbrain DA neurons in PD and highlights the most recent developments in this field.
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影响因子：
2.5
作者：
Bishop, Matthew W.;Chakraborty, Subhojit;Ungless, Mark A.
通讯作者：
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DOI：
10.1073/pnas.0912193106
发表时间：
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作者：
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